Intracarotid cold saline infusion contributes to neuroprotection in MCAO-induced ischemic stroke in rats via serum and glucocorticoid-regulated kinase 1

Abstract

Intracarotid cold saline infusion (IC SI) brings about neuroprotective effects in ischemic stroke. However, the involvement of serum and glucocorticoid-regulated kinase 1 (SGK1) in the underlying mechanism of IC SI is not fully understood; therefore, we used the rat middle cerebral artery occlusion (MCAO) model to investigate the neuroprotective effects of IC SI on ischemic stroke in rats, as well as the involvement of SGK1 in these effects. IC SI decreased infarct size and brain swelling, as determined by 2,3,5-triphenyltetrazolium chloride staining and the dry-wet weight method, respectively. The results of terminal deoxynucleotidyl transferase mediated nick end labeling (TUNEL) and Nissl staining showed that IC SI also suppressed apoptosis and increased the relative integral optical density (IOD) values of Nissl bodies in the rat MCAO model. Regarding the mechanism, the results of immunohistochemistry and western blotting revealed that IC SI upregulated SGK1 expression and downregulated beclin-1 and LC- 3 expression in the rat MCAO model. In addition, SGK1 knockdown increased IC SI- mediated infarct size and brain swelling, promoted apoptosis, and reduced the IOD values of Nissl bodies in the rat MCAO model. In addition, we found that SGK1 knockdown upregulated beclin-1 and LC- 3 expression mediated by IC SI. Overall, IC SI had a neuroprotective effect on ischemic stroke after reperfusion by upregulating SGK1 and inhibiting autophagy.